DESCRIPTION ( Investigator's Abstract): Agentase, LLC seeks Small Business Innovation Research funding to determine the feasibility of using chemically modified enzymes for the treatment and prevention of organophosphorus poisonings. Several known enzymes exhibit hydrolytic activity on target organophosphorus compounds including nerve agent, chemical weapons such as sarin and soman as well as many commercially available pesticides including acute antigenicity, poor enzyme stability, and brief in-vivo residence times. When one considers that annually 3 million cases of severe poisoning and 220,000 deaths worldwide are associated with OP pesticides, there are obviously unmet needs associated with their use. There is a clear need for technology capable of protecting individuals from overexposure to OP compounds. Successful Phase I research will provide proof-of-concept that chemical modification of enzymes alleviates the primary consequences associated with their in-vivo use. Modified OP hydrolyzing enzymes have potential utility as medical treatments for exposed individuals as well as preventative security for individuals at high risk of OP exposure. Such treatments have potential utility at hospitals, agricultural sites employing OP pesticides, civil defense treatment centers for chemical terrorism, and with the armed forces. PROPOSED COMMERCIAL APPLICATION: Enzymatic treatment for the protection of individuals under high risk of exposure to organophosphorus compounds. The technology may also have utility as a medical treatment for individuals contaminated with OP agents. It is potentially useful in the treatment of carbamate and organophosphorus pesticide exposures.